Many applications utilizing fluids such as liquid solvents, aqueous solutions containing dissolved solids, and the like require highly accurate and metered delivery of fluids. As solutions and solvents are generally stored at atmospheric pressure in contact with air, the solutions and solvents become saturated with dissolved air. In the case of dispensing systems, dissolved air can form bubbles within connecting lines, syringes, pumps and detection means as conditions such as temperature and pressure change as the fluid passes through the system. In many systems such as those in clinical analyzers, bubble monitors are used to monitor a dispensed fluid to detect a bubble passing into a volume critical region. A software program may then be triggered to divert the fluid to a waste position, and to then purge the system and re-start the fluid dispensation. If the fluid is a reagent used in a chemical reaction, repeated dispensing of the reagent is both time consuming and costly.
In analytical chemistry, particularly High Pressure Liquid Chromatography (HPLC), it has long been known that the reduction of dissolved air from the mobile phase is of critical importance to the stability of system flow rate and, accordingly, to the proper identification of compounds separated by the HPLC system. Also important to HPLC is the degassing of mobile phase solvents that are blended together using multiple solenoid valves prior to introduction into the inlet of the HPLC pump. This form of HPLC pump design is referred to as “low pressure mixing” in which the HPLC system controller opens and closes solenoid valves associated with each solvent during the intake stroke of the HPLC pump to effect a solvent mixture necessary for developing a chromatogram by the HPLC system. Such low pressure mixing systems are only possible using degassed solvents since the formation of bubbles upon the immediate mixing of the proportioned solvents would otherwise prevent the formation of an accurate solvent composition. An examination into the effect of the change in capacity of a water and alcohol mixture at various concentrations for dissolved oxygen and nitrogen (air) is discussed in Tokunaga, J Chem & Eng Data, Vol 20, No 1, 1975. A conversion of the molar basis for this phenomenon from Molar concentration to percentages by the inventors reveals the relationship used over the years to determine efficiency of removal of the components of air in liquids necessary to mitigate outgassing. Generally, it is desirable to eliminate greater than 62% of the air dissolved in each solvent such that the degassed solvents may be mixed together without the amount of air contributed from any one solvent causing outgassing and bubble formation in the mixture.
Bubble formation during the intake stroke on an HPLC pump may also be limited or prevented by suitable degassing of the mobile phase. Typical HPLC pumps contain a check valve at the inlet, wherein cavitation during the intake stroke may lower the local pressure within the pump chamber to a point at which a gas-saturated solvent will form bubbles. Such bubble formation can prevent the check valve from properly sealing when the pump piston compresses the fluid contained in the pumping chamber. Improper check valve sealing may completely stop the pumping action and therefore prevent the chromatograph from operating. Any small degradation of the performance of the pumping system caused by bubbles is highly undesirable and must be eliminated by sufficiently degassing the solvents so that cavitation within the pumping system does not occur. For this reason, a low flow restriction in each of the proportioning valve system, the degassing chamber, and connection tubing is desired.
In the case of high pressure mixing HPLC, two or more high pressure pumps are typically used with a variable pumping rate to form a predetermined mixture of solvents at a Tee junction upstream from the injection system and HPLC column. Since such solvent mixing occurs at the outlet of the pumps, the system pressure is sufficiently high to prevent bubble formation at the mixing point or through the HPLC separation column. Degassing solvent supplied to these HPLC systems ahead of each pump may be used to eliminate cavitation during the intake stroke of the pump and to eliminate outgassing in a detector operating downstream from the outlet of the HPLC column.
In addition to preventing cavitation in both high-pressure and low-pressure mixing type HPLC systems, mobile phase degassing may also prevent undesired effects at the detector. Mass spectrometric detection requires a smooth, continuous flow of solvent into the nebulizer, which solvent flow can be interrupted by bubbles exiting the column when the solvent is improperly degassed. Moreover, detection of fluorescent compounds eluting from the HPLC column can be quenched by the presence of oxygen in the mobile phase. Background absorbance of solvents such as alcohols, tetrahydrofuran and others can interfere with accurate analyte assessment, and such background absorbance may be mitigated by reducing the concentration of oxygen in the mobile phase to a constant value. In analyses wherein the amount of oxygen present in the system affects detection, control of the concentration of dissolved oxygen to a constant value is beneficial.
Liquid degassing utilizing tubular gas/liquid separation membrane structures for conducting fluid through a degassing chamber have been described previously in, for example, U.S. Pat. Nos. 6,248,157, 6,309,444, 5,885,332, 6,675,835, 7,713,331, 6,949,132, and 6,494,938, assigned to the present assignee and herein incorporated by reference.
While conventional liquid degassing systems employing a semi-permeable membrane are available, there remains a need, particularly with devices associated with liquid chromatography, to provide a fluid degassing capability wherein the combined elements of the degassing system offer low flow restriction, high efficiency, small size and low cost with a reduced footprint when placed within an HPLC instrument. Shortcomings in the prior art have been overcome in the present invention by using a fluid flow distribution arrangement to distribute fluid substantially uniformly across a gas permeable membrane. As it is desirable that the restriction to flow be as low as possible, the relationship between elements along the fluid flow path be arranged such that fluid distribution across the entire surface of the membrane may be substantially uniform at all design flow rates.
A gas-liquid contactor as it is commonly applied in the field of High Pressure Liquid Chromatography (HPLC) or Liquid Chromatography (LC) is configured such that a first side of an inert, gas permeable membrane is in contact with an HPLC mobile phase (mobile phase) comprised of a solvent, or a mixture of solvents, while the opposite, second side of the membrane is in contact with a gas that may be at reduced atmospheric pressure (a vacuum). The function of the membrane is to allow diffusion of atmospheric gas dissolved in the mobile phase into the permeate side of the membrane in a manner consistent with Henry's law and Dalton's law wherein the membrane itself behaves according to Fick's law of diffusion. Of particular interest in the field of HPLC mobile phase degassing is the role of the membrane in selectively allowing atmospheric fixed gasses such as oxygen, nitrogen and carbon dioxide which may be dissolved in the mobile phase to pass through the membrane while restricting the movement of the desired liquid components of the mobile phase from passing through the membrane. Such restriction of movement is commonly referred to as the selectivity of the membrane. It is therefore desirable to select a membrane material which allows the passage of these fixed gasses to the exclusion of the liquid components of the mobile phase.
Fluid degassing in HPLC applications has most predominantly been accomplished through the use of tubular membranes and tubular membrane bundles that convey the mobile phase through their lumens in a reduced atmospheric pressure (vacuum) environment, so that gaseous species within the conveyed fluid is promoted to pass through the luminal walls of the tubular membranes. Such tubular membranes, however, have limitations in their wall thickness, which limits degassing capabilities. Moreover, potting of tubular membranes and tubular membrane bundles can be difficult. In high-flow regimes, flat sheet form membranes may be preferred for their thinness and ease of application.
Though flat-sheet form membrane degassing devices have been proposed, it has been found by the Applicant that conventional configurations fail to fully take advantage of the performance that flat film-form membrane degassing offers. In particular, typical approaches fail to establish a uniform fluid flow field in contact with the membrane, wherein such flow field has a minimal depth to facilitate thorough fluid-membrane contact.
It is therefore an object of the present invention to provide a gas/liquid membrane contactor that yields superior degassing performance in a minimized volume.